Perceived Discrimination and Cardiometabolic Risk Among US Hispanics/Latinos in the HCHS/SOL Sociocultural Ancillary Study.

BACKGROUND: Metabolic syndrome (MetS) is a group of cardiovascular risk factors including elevated blood pressure, elevated triglycerides, decreased high-density lipoprotein cholesterol, impaired fasting glucose, and abdominal obesity, which disproportionately affects Hispanics/Latinos. The present study examined associations between perceived discrimination and MetS in Hispanic/Latino adults from various background groups (i.e., Dominican, Central American, Cuban, Mexican, Puerto Rican, South American). METHODS: Data were obtained from 5174 Hispanics/Latinos who participated in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study. MetS components and covariates were measured at a baseline examination, and perceived discrimination was assessed within 9 months of baseline. Path analysis modeled associations of perceived discrimination with MetS prevalence and each of the six components of MetS, controlling for age, sex, income, acculturation, physical activity, diet, smoking, and alcohol use. RESULTS: Among the full cohort, perceived discrimination was not associated with MetS prevalence in any of the models evaluated. Higher perceived discrimination at work/school was associated with larger waist circumference. When examining background groups separately, higher perceived ethnicity-associated threat was related to increased MetS prevalence only among individuals of Central American background. Differential patterns of association between perceived discrimination and MetS components were found for different background groups. CONCLUSIONS: Overall results suggested that perceived discrimination was not strongly or consistently associated with MetS among Hispanics/Latinos.

Serologic Reactivity Reflects Clinical Expression of Ulcerative Colitis in Children.

Background: In contrast to pediatric Crohn's disease (CD), little is known in pediatric ulcerative colitis (UC) about the relationship between disease phenotype and serologic reactivity to microbial and other antigens. Aim: The aim of this study was to examine disease phenotype and serology in a well-characterized inception cohort of children newly diagnosed with UC during the PROTECT Study (Predicting Response to Standardized Pediatric Colitis Therapy). Methods: Patients were recruited from 29 participating centers. Demographic, clinical, laboratory, and serologic (pANCA, ASCA IgA/IgG, Anti-CBir1, and Anti-OmpC) data were obtained from children 4-17 years old with UC. Results: Sixty-five percent of the patients had positive serology for pANCA, with 62% less than 12 years old and 66% 12 years old or older. Perinuclear anti-neutrophil cytoplasmic antibodies did not correspond to a specific phenotype though pANCA ≥100, found in 19%, was strongly associated with pancolitis (P = 0.003). Anti-CBir1 was positive in 19% and more common in younger children with 32% less than 12 years old as compared with 14% 12 years old or older (P < 0.001). No association was found in any age group between pANCA and Anti-CBir1. Relative rectal sparing was more common in +CBir1, 16% versus 7% (P = 0.02). Calprotectin was lower in Anti-CBir1+ (Median [IQR] 1495 mcg/g [973-3333] vs 2648 mcg/g [1343-4038]; P = 0.04). Vitamin D 25-OH sufficiency was associated with Anti-CBir1+ (P = 0.0009). Conclusions: The frequency of pANCA in children was consistent with adult observations. High titer pANCA was associated with more extensive disease, supporting the idea that the magnitude of immune reactivity may reflect disease severity. Anti-CBir1+ was more common in younger ages, suggesting host-microbial interactions may differ by patient age.

Is there a link between wealth and cardiovascular disease risk factors among Hispanic/Latinos? Results from the HCHS/SOL sociocultural ancillary study.

OBJECTIVE: To examine the relationship between wealth and cardiovascular disease risk factors among Hispanic/Latinos of diverse backgrounds. DESIGN: This cross-sectional study used data from 4971 Hispanic/Latinos, 18-74 years, who participated in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) baseline exam and the HCHS/SOL Sociocultural Ancillary Study. Three objectively measured cardiovascular disease risk factors (hypertension, hypercholesterolemia, and obesity) were included. Wealth was measured using an adapted version of the Home Affluence Scale, which included questions regarding the ownership of a home, cars, computers, and recent vacations. RESULTS: After adjusting for traditional socioeconomic indicators (income, employment, education), and other covariates, we found that wealth was not associated with hypertension, hypercholesterolemia or obesity. Analyses by sex showed that middle-wealth women were less likely to have hypercholesterolemia or obesity. Analyses by Hispanic/Latino background groups showed that while wealthier Central Americans were less likely to have obesity, wealthier Puerto Ricans were more likely to have obesity. CONCLUSION: This is the first study to explore the relationship between wealth and health among Hispanic/Latinos of diverse backgrounds, finding only partial evidence of this association. Future studies should utilize more robust measures of wealth, and address mechanisms by which wealth may impact health status among Hispanic/Latinos of diverse backgrounds in longitudinal designs.

Incorporating Patient Preferences into Estimation of Optimal Individualized Treatment Rules.

Precision medicine seeks to provide treatment only if, when, to whom, and at the dose it is needed. Thus, precision medicine is a vehicle by which healthcare can be made both more effective and efficient. Individualized treatment rules operationalize precision medicine as a map from current patient information to a recommended treatment. An optimal individualized treatment rule is defined as maximizing the mean of a pre-specified scalar outcome. However, in settings with multiple outcomes, choosing a scalar composite outcome by which to define optimality is difficult. Furthermore, when there is heterogeneity across patient preferences for these outcomes, it may not be possible to construct a single composite outcome that leads to high-quality treatment recommendations for all patients. We simultaneously estimate the optimal individualized treatment rule for all composite outcomes representable as a convex combination of the (suitably transformed) outcomes. For each patient, we use a preference elicitation questionnaire and item response theory to derive the posterior distribution over preferences for these composite outcomes and subsequently derive an estimator of an optimal individualized treatment rule tailored to patient preferences. We prove that as the number of subjects and items on the questionnaire diverge, our estimator is consistent for an oracle optimal individualized treatment rule wherein each patient's preference is known a priori. We illustrate the proposed method using data from a clinical trial on antipsychotic medications for schizophrenia.

Association of Serum Lipids and Obstructive Lung Disease in Hispanic/Latino Adults of Diverse Backgrounds.

RATIONALE: Substantial variation in the prevalences of obstructive lung disease exist between Hispanic/Latino heritage groups. Experimental studies have posited biological mechanisms linking serum lipids and lipid-lowering medications with obstructive lung disease. The aim of this study is to examine the associations of serum lipid levels with the prevalences of asthma and chronic obstructive pulmonary disease in the Hispanic Community Health Study/Study of Latinos and how these associations vary by Hispanic/Latino heritage group. METHODS: The Hispanic Community Health Study/Study of Latinos is a population-based probability sample of 16,415 self-identified Hispanic/Latino persons aged 18-74 years recruited between 2008 and 2011 from randomly selected households in four US field centers. The baseline clinical examination included comprehensive biological testing (fasting serum lipid levels), behavioral and socio-demographic assessments, medication inventory including inhalers, and respiratory data including questionnaires for asthma and standardized spirometry with post-bronchodilator measures for identification of obstructive lung disease. MEASUREMENTS AND MAIN RESULTS: Hispanic/Latinos with current asthma had lower age- and statin-use-adjusted mean serum total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels than their non-asthmatic counterparts. In analysis adjusted for age plus gender, ethnicity, cigarette smoking, alcohol intake, body mass index, lipid/cholesterol-lowering medications, age at immigration, health insurance status, and use of oral corticosteroids, increasing serum levels of total cholesterol and low-density lipoprotein cholesterol were associated with lower odds of current asthma in the estimated population. Unlike asthma, Hispanic/Latinos with chronic obstructive pulmonary disease had lower mean high-density lipoprotein than their non- chronic obstructive pulmonary disease counterparts. In the fully adjusted analysis no significant associations were found between lipid levels and prevalent chronic obstructive pulmonary disease. CONCLUSIONS: We showed a modest inverse relationship between serum lipid levels and current asthma. These results highlight some important differences in Hispanics/Latinos and certain serum lipids may be factors or markers of obstructive lung disease.

Associations Between Midlife Vascular Risk Factors and 25-Year Incident Dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort.

Importance: Vascular risk factors have been associated with cognitive decline. Midlife exposure to these factors may be most important in conferring late-life risk of cognitive impairment. Objectives: To examine Atherosclerosis Risk in Communities (ARIC) participants in midlife and to explore associations between midlife vascular risk factors and 25-year dementia incidence. Design, Setting, and Participants: This prospective cohort investigation of the Atherosclerosis Risk in Communities (ARIC) Study was conducted from 1987-1989 through 2011-2013. The dates of this analysis were April 2015 through August 2016. The setting was ARIC field centers (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis suburbs, Minnesota). The study comprised 15 744 participants (of whom 27.1% were black and 72.9% white) who were aged 44 to 66 years at baseline. Main Outcomes and Measures: Demographic and vascular risk factors were measured at baseline (obesity, smoking, diabetes, prehypertension, hypertension, and hypercholesterolemia) as well as presence of the APOE ε4 genotype. After the baseline visit, participants had 4 additional in-person visits, for a total of 5 in-person visits, hospitalization surveillance, telephone calls, and repeated cognitive evaluations. Most recently, in 2011-2013, through the ARIC Neurocognitive Study (ARIC-NCS), participants underwent a detailed neurocognitive battery, informant interviews, and adjudicated review to define dementia cases. Additional cases were identified through the Telephone Interview for Cognitive Status-Modified or informant interview, for participants not attending the ARIC-NCS visit, or by an International Classification of Diseases, Ninth Revision dementia code during a hospitalization. Fully adjusted Cox proportional hazards regression was used to evaluate associations of baseline vascular and demographic risk factors with dementia. Results: In total, 1516 cases of dementia (57.0% female and 34.9% black, with a mean [SD] age at visit 1 of 57.4 [5.2] years) were identified among 15 744 participants. Black race (hazard ratio [HR], 1.36; 95% CI, 1.21-1.54), older age (HR, 8.06; 95% CI, 6.69-9.72 for participants aged 60-66 years), lower educational attainment (HR, 1.61; 95% CI, 1.28-2.03 for less than a high school education), and APOE ε4 genotype (HR, 1.98; 95% CI, 1.78-2.21) were associated with increased risk of dementia, as were midlife smoking (HR, 1.41; 95% CI, 1.23-1.61), diabetes (HR, 1.77; 95% CI, 1.53-2.04), prehypertension (HR, 1.31; 95% CI, 1.14-1.51), and hypertension (HR, 1.39; 95% CI, 1.22-1.59). The HR for dementia for diabetes was almost as high as that for APOE ε4 genotype. Conclusions and Relevance: Midlife vascular risk factors are associated with increased risk of dementia in black and white ARIC Study participants. Further studies are needed to evaluate the mechanism of and opportunities for prevention of the cognitive sequelae of these risk factors in midlife.

Spirometry Reference Equations from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos).

RATIONALE: Accurate reference values for spirometry are important because the results are used for diagnosing common chronic lung diseases such as asthma and chronic obstructive pulmonary disease, estimating physiologic impairment, and predicting all-cause mortality. Reference equations have been established for Mexican Americans but not for others with Hispanic/Latino backgrounds. OBJECTIVES: To develop spirometry reference equations for adult Hispanic/Latino background groups in the United States. METHODS: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) recruited a population-based probability sample of 16,415 Hispanics/Latinos aged 18-74 years living in the Bronx, Chicago, Miami, and San Diego. Participants self-identified as being of Puerto Rican, Cuban, Dominican, Mexican, or Central or South American background. Spirometry was performed using standardized methods with central quality control monitoring. Spirometric measures from a subset of 6,425 never-smoking participants without respiratory symptoms or disease were modeled as a function of sex, age, height, and Hispanic/Latino background to produce background-specific reference equations for the predicted value and lower limit of normal. MEASUREMENTS AND MAIN RESULTS: Dominican and Puerto Rican Americans had substantially lower predicted and lower limit of normal values for FVC and FEV1 than those in other Hispanic/Latino background groups and also than Mexican American values from NHANES III (Third National Health and Nutrition Examination Survey). CONCLUSIONS: For patients of Dominican and Puerto Rican background who present with pulmonary symptoms in clinical practice, use of background-specific spirometry reference equations may provide more appropriate predicted and lower limit of normal values, enabling more accurate diagnoses of abnormality and physiologic impairment.

Association of systemic inflammation, adiposity, and metabolic dysregulation with asthma burden among Hispanic adults.

RATIONALE: Obesity-related asthma is associated with higher disease burden than normal-weight asthma among Hispanics. Adiposity, metabolic dysregulation, and inflammation are all implicated in pathogenesis of obesity-related asthma, but their independent contributions are poorly understood. OBJECTIVE: To examine the independent contributions of body fat distribution, metabolic abnormalities and inflammation on asthma symptoms and pulmonary function among Hispanics. METHODS: Participants of the Hispanic Community Health Study/Study of Latinos with doctor-diagnosed asthma who completed an asthma symptom questionnaire and performed a valid spirometry were included in the analysis (n = 1126). Multivariate analysis was used to examine the independent association of general adiposity (assessed using body mass index), truncal adiposity (assessed by waist circumference), metabolic dysregulation (presence of insulin resistance and low HDL) and inflammation (high-sensitivity C-Reactive Protein≥3 mg/L) with reported asthma symptoms or pulmonary function measures (FEV1, and FVC) while adjusting for demographic and clinical covariates. RESULTS: Of the 1126 participants, 334 (29.5%) were overweight, and 648 (57.8%) were obese. FEV1 and FVC were lower in obese compared to normal-weight asthmatics. In analyses controlling for metabolic and adiposity factors, high hs-CRP (>7 mg/L) was associated with more symptoms (prevalence-ratio 1.27 (95%CI 1.05, 1.54), and lower FVC (ß -138 ml (95%CI -27 ml, -249 ml)) and FEV1 (ß -155 ml (95% CI -38 ml, -272 ml). Low HDL was also associated with lower FVC (ß -111 ml (-22 ml, -201 ml) and FEV1 (ß -100 ml (-12 ml, -188 ml)). Results were similar in men and women. CONCLUSIONS: Our findings suggest that hs-CRP and low HDL, rather than general and truncal adiposity, are associated with asthma burden among overweight and obese Hispanic adults.

Machismo, Marianismo, and Negative Cognitive-Emotional Factors: Findings From the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study.

There is limited research on the traditional Hispanic male and female gender roles of machismo and marianismo, respectively, in relation to negative cognitions and emotions. Given the vulnerability of Hispanics to negative cognitions and emotions, it is important to examine sociocultural correlates of emotional distress. Therefore, we examined associations of machismo and marianismo with negative cognitive-emotional factors (i.e., depression symptoms; cynical hostility; and trait anxiety and anger) in the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study, a cross-sectional cohort study of sociocultural and psychosocial correlates of cardiometabolic health. Participants were aged 18-74 years and self-identified as Hispanic of Central American, Cuban, Dominican, Mexican, Puerto Rican, South American, and other Hispanic background (N = 4,426). Results revealed that specific components of machismo (traditional machismo) and marianismo (family and spiritual pillar dimensions) were associated with higher levels of negative cognitions and emotions after adjusting for socio-demographic factors (p < .05); these associations remained consistent across sex, Hispanic background group, and acculturation. Findings can inform mental health interventions and contribute to our understanding of the importance of gender role socialization in the context of self-reported negative cognitive-emotional factors in Hispanics.

Relationship between body fat and BMI in a US hispanic population-based cohort study: Results from HCHS/SOL.

OBJECTIVE: To evaluate the percentage of body fat (%BF)-BMI relationship, identify %BF levels corresponding to adult BMI cut points, and examine %BF-BMI agreement in a diverse Hispanic/Latino population. METHODS: %BF by bioelectrical impedance analysis was corrected against %BF by (18) O dilution in 434 participants of the ancillary Hispanic Community Health Study/Study of Latinos. Corrected %BF was regressed against 1/BMI in the parent study (n = 15,261), fitting models for each age group, by sex, and Hispanic/Latino background; predicted %BF was then computed for each BMI cut point. RESULTS: Bioelectrical impedance analysis underestimated %BF by 8.7 ± 0.3% in women and 4.6 ± 0.3% in men (P < 0.0001). The %BF-BMI relationship was nonlinear and linear for 1/BMI. Sex- and age-specific regression parameters between %BF and 1/BMI were consistent across Hispanic/Latino backgrounds (P > 0.05). The precision of the %BF-1/BMI association weakened with increasing age in men but not women. The proportion of participants classified as nonobese by BMI but as having obesity by %BF was generally higher among women and older adults (16.4% in women vs. 12.0% in men aged 50-74 years). CONCLUSIONS: %BF was linearly related to 1/BMI with consistent relationship across Hispanic/Latino backgrounds. BMI cut points consistently underestimated the proportion of Hispanics/Latinos with excess adiposity.

Occupational Physical Activity and Body Mass Index: Results from the Hispanic Community Health Study/Study of Latinos.

PURPOSE: To examine the associations between overweight/obesity and occupation among Hispanics/Latinos, the largest minority population in the U.S. METHODS: This study included 7,409 employed individuals in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a prospective study of Hispanic/Latino individuals aged 18-74 in four communities in the U.S. We independently examined the relationships between BMI, Occupational Activity (OA), and Total Hours Worked, quantified via self-reported hours worked per week and occupation-assigned Metabolic Equivalents (METs). RESULTS: More than three quarters of the participants were either overweight (39.3%) or obese (37.8%). Individuals with a primary occupation and those employed in a secondary occupation worked an average of 36.8 and 14.6 hrs/wk, respectively. The overall adjusted odds for being obese compared to normal weight were 3.2% (AOR = 1.03, 95% CI 1.01, 1.05) and 14.4% (AOR = 1.14 95% Cl 1.07, 1.23) greater for each 10 MET•hrs/wk unit of increased OA, and each 10-hrs/wk unit of Total Hours Worked, respectively. CONCLUSION: This study presents the first findings on the association between OA with overweight/obesity among Hispanic/Latino individuals in the U.S. Increasing OA and Total Hours Worked per week were independently associated with increasing odds of overweight/obesity suggesting that the workplace is only one part of the overall energy expenditure dynamic. Our findings point to the need to emphasize engaging employed individuals in greater levels of PA outside of the work environment to impact overweight/obesity.

Pulmonary Disease and Age at Immigration among Hispanics. Results from the Hispanic Community Health Study/Study of Latinos.

RATIONALE: Asthma has been reported to be more prevalent among Hispanics of Puerto Rican heritage than among other Hispanics and among Hispanics born in the United States or who immigrated as children than among those who came as adults; however, direct comparisons across Hispanic groups are lacking. OBJECTIVES: To test whether asthma is more prevalent among Hispanics of Puerto Rican heritage than among other Hispanic groups, whether asthma is associated with age of immigration, and whether chronic obstructive pulmonary disease varies by heritage in a large, population-based cohort of Hispanics in the United States. METHODS: The Hispanic Community Health Study/Study of Latinos researchers recruited a population-based probability sample of 16,415 Hispanics/Latinos, 18-74 years of age, in New York City, Chicago, Miami, and San Diego. Participants self-reported Puerto Rican, Cuban, Dominican, Mexican, Central American, or South American heritage; birthplace; and, if relevant, age at immigration. A respiratory questionnaire and standardized spirometry were performed with post-bronchodilator measures for those with airflow limitation. MEASUREMENTS AND MAIN RESULTS: The prevalence of physician-diagnosed asthma among Puerto Ricans (36.5%; 95% confidence interval, 33.6-39.5%) was higher than among other Hispanics (odds ratio, 3.9; 95% confidence interval, 3.3-4.6). Hispanics who were born in the mainland United States or had immigrated as children had a higher asthma prevalence than those who had immigrated as adults (19.6, 19.4, and 14.1%, respectively; P < 0.001). Current asthma, bronchodilator responsiveness, and wheeze followed similar patterns. Chronic obstructive pulmonary disease prevalence was higher among Puerto Ricans (14.1%) and Cubans (9.8%) than among other Hispanics (<6.0%), but it did not vary across Hispanic heritages after adjustment for smoking and prior asthma (P = 0.22), by country of birth, or by age at immigration. CONCLUSIONS: Asthma was more prevalent among Puerto Ricans, other Hispanics born in the United States, and those who had immigrated as children than among other Hispanics. In contrast, the higher prevalence of chronic obstructive pulmonary disease among Puerto Ricans and Cubans was largely reflective of differential smoking patterns and asthma.

Physical Activity Levels in U.S. Latino/Hispanic Adults: Results From the Hispanic Community Health Study/Study of Latinos.

INTRODUCTION: Physical activity (PA) prevalence among U.S. Latino/Hispanic adults of diverse backgrounds is not well known. This study describes PA among a representative sample of U.S. Latino/Hispanic adults. METHODS: A population-based cohort of Hispanic/Latino adults (aged 18-74 years) participating in the Hispanic Community Health Study/Study of Latinos from March 2008 to June 2011 (N=16,415) was recruited in four urban areas from Miami, the Bronx, Chicago, and San Diego. Participants wore an Actical hip accelerometer for 1 week (n=12,253) and completed the Global Physical Activity Questionnaire (n=15,741). Data were analyzed in 2015. RESULTS: Based on accelerometry, Hispanics/Latinos engaged in 23.8 minutes/day (10.3 minutes/day when only considering minutes from sustained 10-minute bouts) of moderate to vigorous PA (MVPA). Individuals of Puerto Rican and Dominican background had the most minutes/day of MVPA (32.1 and 29.1, respectively), whereas those of Cuban background had the fewest (15.3). Based on the Global Physical Activity Questionnaire, 65% of Hispanic/Latinos met the aerobic component of 2008 Physical Activity Guidelines for Americans. Men and individuals of Puerto Rican background had the most minutes/day of leisure-time MVPA (30.3 and 30.2, respectively). Individuals of Puerto Rican and Dominican background had the most minutes/day of transportation-related PA (48.7 and 39.7, respectively). Individuals of Mexican and Central American background had the most minutes/day of work-related MVPA (90.7 and 93.2, respectively). CONCLUSIONS: Among Hispanics/Latinos, self-reported data provided information on the type of PA and helped explain variability identified from accelerometer-assessed PA. These findings highlight variability in PA among Hispanics from diverse ethnic backgrounds.

Neurocognitive function among middle-aged and older Hispanic/Latinos: results from the Hispanic Community Health Study/Study of Latinos.

We sought to examine and describe neurocognitive function among middle-aged and older Hispanic/Latino Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants. We analyzed baseline cross-sectional data from the middle-aged and older (ages 45-74 years old) participants (n = 9,063) to calculate neurocognitive function scores and their correlates. Older age and higher depressive symptoms scores were associated with lower average neurocognitive performance, whereas greater educational attainment and household income were associated with higher neurocognitive performance. Hispanic/Latino heritage groups significantly varied in neurocognitive performances. Some neurocognitive differences between Hispanics/Latinos were maintained after controlling for language preference, education, household income, and depressive symptoms. We found notable differences in neurocognitive scores between Hispanic/Latino heritage groups that were not fully explained by the cultural and socioeconomic correlates examined in this study. Further investigations into plausible biological and environmental factors contributing to the Hispanic/Latino heritage group differences in neurocognitive found in the HCHS/SOL are warranted.

Comparison of serum, EDTA plasma and P100 plasma for luminex-based biomarker multiplex assays in patients with chronic obstructive pulmonary disease in the SPIROMICS study.

BACKGROUND: As a part of the longitudinal Chronic Obstructive Pulmonary Disease (COPD) study, Subpopulations and Intermediate Outcome Measures in COPD study (SPIROMICS), blood samples are being collected from 3200 subjects with the goal of identifying blood biomarkers for sub-phenotyping patients and predicting disease progression. To determine the most reliable sample type for measuring specific blood analytes in the cohort, a pilot study was performed from a subset of 24 subjects comparing serum, Ethylenediaminetetraacetic acid (EDTA) plasma, and EDTA plasma with proteinase inhibitors (P100). METHODS: 105 analytes, chosen for potential relevance to COPD, arranged in 12 multiplex and one simplex platform (Myriad-RBM) were evaluated in duplicate from the three sample types from 24 subjects. The reliability coefficient and the coefficient of variation (CV) were calculated. The performance of each analyte and mean analyte levels were evaluated across sample types. RESULTS: 20% of analytes were not consistently detectable in any sample type. Higher reliability and/or smaller CV were determined for 12 analytes in EDTA plasma compared to serum, and for 11 analytes in serum compared to EDTA plasma. While reliability measures were similar for EDTA plasma and P100 plasma for a majority of analytes, CV was modestly increased in P100 plasma for eight analytes. Each analyte within a multiplex produced independent measurement characteristics, complicating selection of sample type for individual multiplexes. CONCLUSIONS: There were notable detectability and measurability differences between serum and plasma. Multiplexing may not be ideal if large reliability differences exist across analytes measured within the multiplex, especially if values differ based on sample type. For some analytes, the large CV should be considered during experimental design, and the use of duplicate and/or triplicate samples may be necessary. These results should prove useful for studies evaluating selection of samples for evaluation of potential blood biomarkers.

Impact of second-generation antipsychotics and perphenazine on depressive symptoms in a randomized trial of treatment for chronic schizophrenia.

BACKGROUND: According to the American Psychiatric Association Clinical Practice Guidelines for schizophrenia, second-generation antipsychotics may be specifically indicated for the treatment of depression in schizophrenia. We examined the impact of these medications on symptoms of depression using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), conducted between January 2001 and December 2004. METHOD: Patients with DSM-IV-defined schizophrenia (N = 1,460) were assigned to treatment with a first-generation antipsychotic (perphenazine) or one of 4 second-generation drugs (olanzapine, quetiapine, risperidone, or ziprasidone) and followed for up to 18 months (phase 1). Patients with tardive dyskinesia were excluded from the randomization that included perphenazine. Depression was assessed with the Calgary Depression Scale for Schizophrenia (CDSS). Mixed models were used to evaluate group differences during treatment with the initially assigned drug. An interaction analysis evaluated differences in drug response by whether patients had a baseline score on the CDSS of ≥ 6, indicative of a current major depressive episode (MDE). RESULTS: There were no significant differences between treatment groups on phase 1 analysis, although there was a significant improvement in depression across all treatments. A significant interaction was found between treatment and experiencing an MDE at baseline (P = .05), and further paired comparisons suggested that quetiapine was superior to risperidone among patients who were in an MDE at baseline (P = .0056). CONCLUSIONS: We found no differences between any second-generation antipsychotic and the first-generation antipsychotic perphenazine and no support for the clinical practice recommendation, but we did detect a signal indicating a small potential difference favoring quetiapine over risperidone only in patients with an MDE at baseline.

Treatment outcomes of patients with tardive dyskinesia and chronic schizophrenia.

OBJECTIVE: We compared the response to antipsychotic treatment between patients with and without tardive dyskinesia (TD) and examined the course of TD. METHOD: This analysis compared 200 patients with DSM-IV-defined schizophrenia and TD and 997 patients without TD, all of whom were randomly assigned to receive one of 4 second-generation antipsychotics. The primary clinical outcome measure was time to all-cause treatment discontinuation, and the primary measure for evaluating the course of TD was change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare treatment discontinuation between groups. Changes in Positive and Negative Syndrome Scale (PANSS) and neurocognitive scores were compared using mixed models and analysis of variance. Treatment differences between drugs in AIMS scores and all-cause discontinuation were examined for those with TD at baseline. Percentages of patients meeting criteria for TD postbaseline or showing changes in AIMS scores were evaluated with χ(2) tests. Data were collected from January 2001 to December 2004. RESULTS: Time to treatment discontinuation for any cause was not significantly different between the TD and non-TD groups (χ(2)(1) = 0.11, P = .743). Changes in PANSS scores were not significantly different (F(1,974) = 0.82, P = .366), but patients with TD showed less improvement in neurocognitive scores (F(1,359) = 6.53, P = .011). Among patients with TD, there were no significant differences between drugs in the decline in AIMS scores (F(3,151) = 0.32, P = .811); 55% met criteria for TD at 2 consecutive visits postbaseline, 76% met criteria for TD at some or all postbaseline visits, 24% did not meet criteria for TD at any subsequent visit, 32% showed a ≥ 50% decrease in AIMS score, and 7% showed a ≥ 50% increase in AIMS score. CONCLUSIONS: Schizophrenia patients with and without TD were similar in time to discontinuation of treatment for any cause and improvement in psychopathology, but differed in neurocognitive response. There were no significant differences between treatments in the course of TD, with most patients showing either persistence of or fluctuation in observable symptoms. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00014001.

Time to All-cause Treatment Discontinuation as the Primary Outcome in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Study.

Time until all-cause treatment discontinuation was the primary outcome of the CATIE trial. We discuss the advantages and disadvantages of this outcome, and evaluate its association with clinical correlates through graphical response profiles. We investigate the characteristics of patients who discontinued for patient decision, including a reclassification of patient decision into other reasons. All-cause discontinuation is compared to a related outcome, time until treatment failure. Patients who discontinued had lower quality of life scores than other patients. Patients discontinuing for lack of efficacy had worsened efficacy scores compared with an improvement for other patients. Those who discontinued for patient decision had lower compliance. Blinded reclassification of discontinuation for patient decision identified 5% of cases as lack of efficacy and 21% as intolerable side effects. Reclassified patients participated in the next study phase at a higher rate than those remaining as patient decision (67% vs. 10%). Treatment group differences for time to discontinuation due to patient decision were attenuated after censoring the reclassified patients, but were still suggestive. Treatment comparisons for time to treatment failure were consistent with all cause discontinuation, although somewhat smaller. All-cause discontinuation is recommended as a simple and comprehensive outcome for pharmaceutical Phase II-IV clinical trials.

The effects of antipsychotic medications on emotion perception in patients with chronic schizophrenia in the CATIE trial.

Few pharmacological intervention studies have examined the impact of medication on social cognition, particularly emotion perception. The goal of this randomized, double-blind study is to compare the effects of several second generation antipsychotics and a first generation antipsychotic, perphenazine, on emotion perception in individuals with schizophrenia. Patients were assigned to receive treatment with olanzapine, queitapine fumarate, risperidone, ziprasidone or perphenazine for up to 18 months. Eight hundred and seventy three patients completed an emotion perception test immediately prior to randomization and after 2 months of treatment. We also examined baseline predictors of emotion perception change. Most treatments were associated with a small, non-statistically significant improvement in emotion perception at two months, although they did not differ from one another. Greater improvement in emotion perception at 2 months was significantly predicted by lower baseline emotion perception and higher baseline neurocognitive functioning, and marginally predicted by less time on an antipsychotic.